Copper(II) Triflate Catalyzed Amination of 1,3‐Dicarbonyl Compounds

Abstract

A method to prepare α,α-acyl amino acid derivatives efficiently by Cu(OTf)(2)+1,10-phenanthroline (1,10-phen)-catalyzed amination of 1,3-dicarbonyl compounds with PhI=NSO(2) Ar is described. The mechanism is thought to initially involve aziridination of the enolic form of the substrate, formed in situ through coordination to the Lewis acidic metal catalyst, by the putative copper-nitrene/imido species generated from the reaction of the metal catalyst with the iminoiodane source. Subsequent ring opening of the resultant aziridinol adduct under the Lewis acidic conditions then provided the α-aminated product. The utility of this method was exemplified by the enantioselective synthesis of a precursor of 3-styryl-2-benzoyl-L-alanine.

Transition metal-free iminoiodane-mediated amination of activated C-H bonds

“…In summary, we have developed a Brønsted acid-catalyzed method to access unnatural α,α-acyl amino acid derivatives from 1,3-dicarbonyl compounds and PhI=NTs. Our studies show the reaction to be applicable to β-keto esters and phosphonates as well as 1,3-diones and complement earlier works that make use of Cu(II) 50 and Zn(II) 98 catalysis.…”

“…Flash chromatography was performed using silica gel and gradient solvent system (eluent: n-hexane:EtOAc). Ethyl 2-(4-methylphenylsulfonamido)-3-oxo-3-phenylpropanoate 62a 50,98 Yield 86%; white solid; 1 H NMR (400 MHz, CDCl 3 ) δ 7.98 (d,J = 7.4 Hz,Ar H,2H) 165.9, 144.1, 144.0, 136.6, 134.7, 129.8, 129.5, 128.9, 127.4, 62.6, 60.9, 21.6, 13.8.…”

“…Ethyl 2-(4-methylphenylsulfonamido)-3-oxo-3-m-tolylpropanoate 62c 50,98 Yield 84%; white solid; 1 H NMR (300 MHz, CDCl 3 ) δ 7.78 (d, J = 7.3 1, 144.0, 138.8, 136.6, 135.4, 133.5, 129.8, 129.7, 128.7, 127.3, 126.6, 62.6, 60.9, 21.5, 21.3, 13.7.…”

“…Ethyl 2-(2-methylphenylsulfonamido)-3-oxo-3-o-tolylpropanoate 62d 50,98 Yield 65%; white solid; 1 7, 176.2, 171.4, 166.0, 143.9, 142.9, 139.9, 137.2, 136.6, 133.7, 132.7, 132.1, 129.7, 129.6, 129.1, 127.3, 127.1, 125.8, 125.0, 100.9, 62.5, 61.6, 60.4, 21.4, 21.1, 19.8, 14.2, 13.8, 13.6.…”

“…In 2012, Chan and co-workers showed β-dicarbonyl compounds could undergo aziridination as the enolate with PhI=NTs. 50 In the presence of copper(II) triflate as Lewis acid as well as the nitrene transfer catalyst and 1,10-phenanthroline as the ligand, the aziridination/ring opening reaction afforded the corresponding α-amino-βdicarbonyl compounds in yields of 53-99% (Scheme 1.13).…”